Tissue arrays, also called tissue microarrays (TMAs), contain a plurality of different tissue samples in a single receiver block or paraffin block. The receiver block is sectioned in the usual manner with a microtome, and the section is applied onto a specimen slide. The specimen slide then contains a plurality of different tissue samples. Because of the large number of tissue samples on a single specimen slide, it is possible to stain or process all the samples under the same conditions. As a result, even very complex and expensive staining methods, for example those derived from immunohistochemistry (IHC) or in-site hybridization (ISH) for revealing DNA or RNA, can be applied effectively.
The production of tissue arrays is very time-consuming, however, since a plurality of different samples (up to 1,000) are arranged next to one another in one receiver block. From the various tissue or sample blocks, a tissue core is punched out with a hollow needle and transferred into a correspondingly prepared receiver block.
Before a tissue core is removed from a sample block, the corresponding site on the sample block must be located and marked. It has proven useful for this purpose, in practice, first to produce usual microtome sections from a sample block, apply them onto specimen slides, stain them using a standard method, and have them inspected by a pathologist. The pathologist then selects the sites of interest on the specimen slide, and marks that site directly on the specimen slide.
The laboratory worker producing the tissue arrays then has the task of locating, on the tissue block or donor block, the sites marked on the specimen slide, and removing a tissue core at the corresponding sites.
Punched-out portions or paraffin cores are also removed, using a hollow needle, from the receiver block, which as a rule is made of paraffin. The tissue cores are then introduced into the cavity thus created. As mentioned, as many as 1,000 tissue cores—depending on the application—can be arranged to form an array on one paraffin block. From these dimensions alone, it is apparent that the diameters of the tissue cores are less than 1 mm, and reliable and simple transfer of the tissue cores into the punched hole in the paraffin block is therefore possible only with special equipment.
An apparatus for producing a tissue array is known from U.S. Pat. No. 6,103,518. This apparatus is characterized in that the receiver block is arranged in stationary fashion, and possesses thereabove a pivotably mounted needle holder for two hollow needles. The needle holder is aligned onto the receiver block by way of an X-Y micrometer displacement device. The two needles—one for punching out the receiver block, the other for removing the tissue core—can be brought alternately into the working position.
For removal of the tissue core from the tissue block, the latter is placed manually, together with a U-shaped frame, above the paraffin block and aligned onto the hollow needle.
With this apparatus, it has proven difficult to locate, on the tissue block, the site marked on the specimen slide, and furthermore to ensure reliable introduction of the tissue core into the paraffin block.
An automated device for producing tissue arrays is known from U.S. Pat. No. 6,383,801 B1. Here both multiple paraffin blocks and multiple tissue blocks are arranged on an X-Y scanning stage. Also provided are two hollow needles operating independently of one another, of which one makes the punched holes in the paraffin block and the other is responsible for tissue core removal.
This device is very complex and moreover does not solve the problem of easily locating a marked site on the tissue block.